Colorectal cancer (CRC) is the 3rd most common malignancy in the US and the third leading cause of cancer death. Compared to European Americans (EA), African Americans (AA) have a substantially higher CRC mortality rate that is a function of both a higher incidence rate and lower survival rate. At least some of the excess mortality in African Americans is caused by the reduced survival associated with a higher prevalence of late stage disease and more metastatic disease at diagnosis compared to EA. However, racial disparities in survival persist even after controlling for stage at diagnosis. The reasons for this are not known, but possible explanations include racial differences in biologic factors, such as the aggressiveness of the primary and/or metastatic tumors, and non-biologic factors such as socioeconomic variables, and or treatment related factors. The primary goal of the research plan is to investigate the combination of age and pathologic and pathomorphologic markers as contributing factors to the racial disparity in CRC survival. Our central hypothesis is that the racial disparity is at least partially driven by younger AA having a greater predispositio to develop more aggressive CRC, which in turn result in poorer response to treatment and hence lower overall survival. We will perform a cross sectional study to collect tumor specimens to provide a comprehensive and accurate summary of the pathologic, pathomorphologic features of primary tumors in AA and EA with CRC. Next, we will perform an analysis to examine the joint influence of race and pathologic and pathomorphologic markers on survival in early and late onset CRC in AA and EA. This study will generate needed evidence to begin to address several important questions regarding the role of pathologic indicators in influencing the differences in survival between AA and EA. The results from the present proposal will serve as preliminary data for a larger-scale study that will enroll patients throughout South Carolina. The larger study to follow will address a suite of questions that will include how biologic and non-biologic indicators impact racial differences in treatment adherence, response to therapy, and overall survival. PUBLIC HEALTH RELEVANCE: Colorectal cancer is the source of significant morbidity and mortality especially among African Americans. Studies, like the one proposed, seek to understand the reasons for racial disparities in colorectal cancer and hence provide insights into the mechanisms of the disease process. We envision the present proposal as part of the larger question of exploring, understanding, and improving outcomes among AA diagnosed with colorectal cancer.